In Brief

This article describes some common drug-drug interactions between prescription medications and over-the-counter medications that people with diabetes might encounter. With each interaction listed, there is a description of how to appropriately manage it. Also, proper timing of the medications in relation to food intake is described. The data presented are not all-inclusive but do detail the common medications used in people with diabetes.

An estimated 17 million people in the United States have diabetes. This is ∼6.2% of the population.1 The majority of the premature deaths attributed to diabetes are a result of complications from the disease.2 Approximately 73% of adults with diabetes have high blood pressure or use prescription medications to help control hypertension. Adults with diabetes are also two to four times more likely to die from heart disease or to have a stroke than are those without diabetes.1 The macrovascular diseases, such as arteriosclerosis, are one of the many reasons for the increased incidence of heart disease and stroke. National guidelines now suggest more stringent blood pressure and cholesterol targets than in the past. Therefore, people with diabetes are more likely to be prescribed multiple medications to control these concurrent disease states.

The greater the number of medications a person is taking, the greater the risk for drug-drug interactions. According to one hospital study,3 33% of all adverse drug reactions (ADRs) were a result of preventable drug interactions. This percentage may be even larger if over-the-counter (OTC) product use were taken into account. Drug interactions between common prescription medications and OTCs that a person with diabetes might encounter will be discussed further in this article. Common classes of prescription medications used in diabetes are antidiabetic agents, antihypertensive agents, and antilipemic agents. Common OTCs include analgesics, cough and cold products, and antacids/laxatives. Drug-drug interactions among these classes of medications, as well as the few drug-disease interactions possible with these agents, will be reviewed.

Thousands of drug-drug interactions have been documented. However, only a small percentage of these are clinically important. To help clinicians determine the clinical significance of a drug interaction, rating systems have been established. Most rating systems use a numerical scale.

This article will draw upon the rating scales developed by Facts and Comparisons4 and Hansten and Horn.5 The two scales stratify drug interactions by their severity and documentation of supporting biomedical literature. Hansten and Horn assess severity and documentation together, whereas Facts and Comparisons assesses each of these individually first and then assigns a rating. Facts and Comparisons’ ratings will be referred to as “significance rating A,” and the rating provided by Hansten and Horn will be referred to as “significance rating B.”

When assessing severity, Facts and Comparisons labels the interactions as Major, Moderate, or Minor. Major interactions are those in which the effect is potentially capable of causing permanent damage. Moderate interactions are those that may cause deterioration in the clinical status of a patient. Minor interactions are those in which the consequences may be bothersome but should not significantly affect outcomes.

Facts and Comparisons categorizes the documentation in the literature as Established, Probable, Suspected, Possible, or Unlikely. Established documentation has been proven to occur in well-controlled studies. Probable documentation is very likely to occur but not proven clinically. Suspected documentation means that it may occur and that there are good data, but that more studies are needed to confirm. Possible documentation means that it may occur, however there is limited data. Unlikely documentation means the interaction is doubtful because there is no good evidence supporting it.

Finally, a numerical rating of 1 to 5 is assigned. A level 1 rating is most severe and has a very high probability of occurring. A level 4 or 5 rating is considered mild and of low probability. Table 1 outlines the stratification and the assigned numerical rating.

The majority of pharmacies throughout the country screen for drug-drug interactions among prescription medications dispensed. Unfortunately, this screening process is not available when OTCs are purchased. Labeling regulations for OTCs require the manufacturers to list potential interactions with medications and disease states.

Certain classes of medications tend to have a higher incidence of drug interactions. According to one hospital study in Germany,6 thiazide diuretics and angiotensin-converting enzyme (ACE) inhibitors had the highest percentage of potential interactions compared to other classes of antihypertensive medications. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) recommends these two classes of medications as preferred agents in people with diabetes. While these medications clearly benefit this patient population, their use also puts this group of patients at higher risk for drug-drug interactions.

Because this patient population is at high risk for cardiovascular events, blood pressure control must be aggressively approached. JNC VI recommends lowering blood pressure in this population to <130/85 mmHg, whereas the American Diabetes Association recommends lowering it to <130/80 mmHg.7,8 People with diabetes and hypertension are more likely to be taking more than one class of antihypertensive medication regardless of the target recommended.

Five classes of antihypertensive medications have been included in this article. ACE inhibitors, β-adrenergic blockers, calcium-channel blockers, loop diuretics, and thiazide diuretics, and their interactions with OTC analgesics and antacids are described. By far, the antihypertensives have more interactions with OTCs than do the two other classes reviewed. Table 2 outlines the interactions, significance ratings assigned, and possible courses of management.

OTC cough and cold medications have more drug-disease interactions than drug-drug interactions. Table 3 outlines the OTCs and their possible negative effects in people with diabetes.

Because people with diabetes are more likely to have high blood glucose, hypertension, and poor circulation, OTCs to be concerned about are those that may increase blood glucose, increase blood pressure, or constrict blood vessels. Decongestants may affect blood pressure and circulation. Cough syrups may contain several different ingredients, including decongestants, and are available with and without added sugar. Therefore, they may alter glucose, circulation, and/or blood pressure. It would be prudent to counsel patients to read labels on these products to identify potential interactions.

A study performed in a U.S. Army Medical Center9 showed no significant adverse effects on blood glucose levels when people with diabetes took sugar-containing cough formulas in short courses. Most health care providers would agree that if a patient’s glucose and blood pressure are stable and reasonably well controlled, the short-term use of OTC cough and cold products should be of little risk.

In summary, the effects of OTCs on patients with diabetes are variable and unpredictable. The best advice is to monitor glucose and blood pressure routinely when starting or stopping any OTC agent and to adjust medications if necessary.

In addition to assessing the potential for drug-drug and drug-disease interactions, diabetes health care professionals must also monitor for drug-food interactions. In other words, what is the most appropriate time to take medications in regard to food intake? Food may hinder absorption or increase absorption of a medication. To obtain the maximum efficacy of a medication, it is helpful to know when the medication should be administered with regard to meals.

As outlined in Table 4, most antidiabetic medications achieve maximum efficacy when taken before meals. Yet, most antihypertensive medications can be taken without regard to food. Generally speaking, if a medication causes stomach upset when taken on an empty stomach, taking it with a little bit of food may hinder the absorption slightly but certainly not as significantly as not taking the medication at all.

In conclusion, medications are prescribed to improve quality and quantity of life. Medications should be effective for the diagnosis, be easy to administer, and cause a minimum of side effects. To achieve maximum efficacy of a medication, drug-drug interactions, drug-disease interactions, and the timing of administration with respect to food should be examined thoroughly before co-administration of multiple medications.

This article provides a reference to aid in this evaluation. The data presented are not all-inclusive but do detail the common issues surrounding medication use in people with diabetes.

Kimberly R. Rhoades, RPh, CDE, is a clinical pharmacist with Kaiser Permanente—Colorado in Lakewood, Colo.

Table 1.

Significance Rating Scales

Significance Rating Scales
Significance Rating Scales
Table 2.

Prescription Drug and OTC Interactions

Prescription Drug and OTC Interactions
Prescription Drug and OTC Interactions
Table 3.

OTC Drug-Disease Interactions

OTC Drug-Disease Interactions
OTC Drug-Disease Interactions
Table 4.

Timing of Administration11 

Timing of Administration11
Timing of Administration11
Miyashiro LA: Diabetes mellitus. In Pharmacotherapy Self Assessment Program. 4th ed. Book 3. Kansas City, Mo. American College of Clinical Pharmacy, p. 113
Ferrill M: Clinically relevant drug interactions. In Drug Facts and Comparisons News. St. Louis, Mo., Facts and Comparisons, Nov. 1999, p. 83–86
Tatro DS: Drug Interaction Facts. St. Louis, Mo., Facts and Comparisons, April 2002
Hansten PD, Horn JR: Drug Interaction Analysis and Management. St. Louis, Mo., Facts and Comparisons, July 1999
Kohler GI, Bode-Boger SM, Busse R, Hoopmann M, Welte T, Boger RH: Drug-drug interactions in medical patients: effects of in-hospital treatment and relation to multiple drug use.
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The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI). NIH Publication No. 98-4080, Nov 1997, p. 49
American Diabetes Association: Treatment of hypertension in adults with diabetes (Position Statement).
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LeMar HJ Jr, Georgitis WJ: Effect of cold remedies on metabolic control of NIDDM.
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Konrad D, Sobetzko D, Schmitt B, Schoenle EJ: Insulin-dependent diabetes mellitus induced by the antitussive agent dextromethorphan (Letter).
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